title: Effects of glucocorticoids on traumatic brain injury related critical illness-related corticosteroid insufficiency.
abstract: BACKGROUND
  Traumatic brain injury (TBI) is a heterogeneous condition that can lead to critical LLLness-related corticosteroid insufficiency (CIRCI) causing a high mortality and morbidity. Glucocorticoids were widely used in the clinical management of TBI, but their benefit has been challenged in some studies and their efficacy, especially for treating CIRCI in TBI patients, remains unclear.
  
  
  METHODS
  We conducted a meta-analysis of published data to determine if the controversy is related to clinical dosing and timing of glucocorticoids (GCs) application. We analyzed published reports in four databases (MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and CBMdisc). The published data were stratified into not only low- and high-dose GCs group but also short- and long-term GCs group to compare their effectiveness in improving TBI outcomes.
  
  
  RESULTS
  We totally identified 16 reports. For low-dose patients, the pooled relative risks (RRs) for two clinical outcomes of death or a combination of death and severe disability were 0.95 (95% confidence interval (CI): 0.80 to 1.13) and 0.95 (95% CI: 0.83 to 1.09), respectively. The risks for infection and gastrointestinal bleeding were 0.85 (95% CI: 0.50 to 1.45) and 0.64 (95% CI: 0.15 to 2.70), respectively. For high-dose group, the pooled RR of death is 1.14 (95% CI: 1.06 to 1.21). The pooled RRs for infection and gastrointestinal bleeding for the high-dose patients were 1.04 (95% CI: 0.93 to 1.15) and 1.26 (95% CI: 0.92 to 1.75), respectively. For long-term use group, the pooled RRs for two clinical outcomes of death or a combination of death and severe disability were 0.98 (95% CI: 0.87 to 1.12) and 1.00 (95% CI: 0.90 to 1.11), respectively. The risks for infection and gastrointestinal bleeding were 0.88 (95% CI: 0.71 to 1.11) and 0.96 (95% CI: 0.35 to 2.66), respectively. For short-term use group, the pooled RR of death is 1.15 (95% CI: 1.07 to 1.23), and importantly the effects on infections were beneficial in terms of TBI patients suffering from CIRCI.
  
  
  CONCLUSIONS
  This meta-analysis suggests an increased risk of death for TBI patients on a high dose and short term of glucocorticoids compared with those on a low dose and long term, for whom a trend towards clinical improvement is evident. In addition, stress-does of GCs further decrease the pneumonia incidence in TBI patients suffering from CIRCI. A large-scale multicenter randomized controlled trial is warranted for testing (1) the efficacy of stress-dose GCs treatment in the sub-acute phase of TBI (4-21 days after initial trauma), when CIRCI is most likely to occur; (2) the hypothesis that stress-dose GCs could boost patients' stress function and ensure survival.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Degeneration and Regeneration of Nervous System, Tianjin 300052, China.
authors.forename: Zi-long
authors.initials: ZL
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.forename: Bao-liang
authors.initials: BL
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chai
authors.forename: Xin-yuan
authors.initials: XY
authors.lastname: Li
authors.forename: Jing-fei
authors.initials: JF
authors.lastname: Dong
authors.forename: Jian-ning
authors.initials: JN
authors.lastname: Zhang
mesh_terms: D000305:Adrenal Cortex Hormones / Q000172:deficiency*; D001930:Brain Injuries / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016638:Critical Illness; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids